Innate immune cell interactions mediated by the SIRP receptor family

在脊椎动物中，多个系统协作以确保识别和消除老化，有缺陷或受感染的细胞，同时保留正常的“自我”组织。免疫稳态需要促进反应的激活受体和维持自身耐受的抑制受体之间的平衡。我的计划的长期目标是了解这些激活和抑制反应是如何整合的，以保持准确的自我/非自我识别。这种相互作用已在介导适应性免疫的淋巴细胞中进行了广泛研究，但在先天免疫细胞如巨噬细胞（M？）中的了解较少。我们已经证明，先天免疫受体信号调节蛋白-α（SIRPα）是一种抑制性受体，它识别几乎所有健康细胞上表达的蛋白质。我建议确定信号通路和下游介质SIRPα抑制M？正常的自我反应，并被调节以允许对非自我细胞的适当反应。

In vertebrates, multiple systems collaborate to ensure recognition and elimination of cells that are aged, defective or infected, while preserving normal “self” tissues. Immune homeostasis requires a balance between activating receptors that promote responses and inhibitory receptors that maintain self-tolerance. The long-term goal of my program is to understand how these activating and inhibitory responses are integrated to maintain accurate self/non-self recognition. This interplay has been studied extensively in lymphocytes that mediate adaptive immunity, but is less well understood in innate immune cells such as macrophages (M?). We have shown that the innate immune receptor Signal Regulatory Protein-α (SIRPα) is an inhibitory receptor that recognizes a protein expressed on virtually all healthy cells. I propose to identify the signalling pathways and down-stream mediators by which SIRPα inhibits M? responses to normal self and is regulated to allow appropriate responses to non-self cells.